METHODS: 14 stable pts (mean age of 69.6 yrs, HD vintage > 3 mo, solely a-v fistulas, 0.70 6 0.04 mg/kg of ENX per HD) constituted a self-control group. First, their longterm polysulfone dialyzers were switched to the anti-thrombogenic heparin-grafted HeprAN hydrogel membranes (Evodial) and the usual bolus dose of ENX was injected (ENX-HD). Blood for immunoreactive Scl quantification (by EIA kits from TECOmedical AG) was collected before onset of HD and heparinization (T0), and again after 10

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... 10), 30 (T30) and 120 minutes (T120). At T30, the effluent dialysate was also sampled directly after the dialyzer. The consecutive HD session was performed also with the use of the HeprAN membrane, but without systemic ENX administration (NoHep-HD). Blood and dialysate flow rate, prescribed ultrafiltration (UF) volume and dialysate temperature were kept equal, with no UF or Na profiling. RESULTS: During the ENX-HD plasma Scl levels fluctuated and were: 1.59 6 0.19 ng/ ml at T0, 2.04 6 23 ng/ml at T10, 1.48 6 0.18 ng/ml at T30, and 1.16 6 0.14 ng/ml at T120 (ANOVA F ¼ 3.74, P ¼ 0.016). The peak T10 Scl levels were higher only vs Scl levels at T120 (by 75.9%, P ¼ 0.009). The percentage of change (D) in plasma Scl at T10 vs T0 was directly associated with the dose of ENX (rho ¼ 0.598, P ¼ 0.024). A robust direct association between D plasma Scl T120 vs T10 decline and UF volume at T120 was found (r ¼ 0.667, P ¼ 0.008). During the NoHep-HD plasma Scl levels gradually and steadily decreased and were: 1.57 6 0.17 ng/ml at T0, 1.40 6 0.16 ng/ml at T10, 1.18 6 0.12 ng/ml at T30 and 0.96 6 0.10 ng/ml at T120 (ANOVA F ¼ 3.57, P ¼ 0.033). The T120 Scl levels were lower than those at T0 by 38.9% (P ¼ 0.017). The D Scl decrease at T120 vs T0 was again directly associated with the T120 UF volume (r ¼ 0.717, P ¼ 0.004). The predialytic (T0) plasma Scl levels did not differ between the two HD procedures (P ¼ 0.850). All the overdialytic plasma Scl levels during the ENX-HD were higher than the corresponding ones during the NoHep-HD (all P < 0.009). The Scl levels measured in dialysate obtained at T30 did not differ between the procedures. CONCLUSIONS: During traditional HD, sclerostin is released into circulating blood by enoxaparin and removed form circulation via dialyzer. It is biologically plausible that such procedures, particularly when repeated for months or years, deplete vascular wall from its calcification inhibitor and thus promote VC. This novel effect of enoxaparin (and likely -other heparins) may essentially supplement the conundrum of Scl significance in maintenance HD population.